1. Field of the Invention
The present invention relates to N-adamantane-substituted tetrapeptide amides and the pharmacologically acceptable salts thereof. These compounds are analogs of enkephalin wherein the methionine or leucine of position 5 has been substituted by an adamantyl amide and the glucine of position 2 has been substituted by various amino acid residues. Optionally, the tyrosine of position 1 and the phenylalanine of position 4 may also be substituted by various amino acid residues. Enkephalin, a naturally occurring pentapeptide, has been isolated and found to be a mixture of two pentapeptides which differ only in the fifth amino acid residue. Leucine .sup.5 -enkephalin is represented by the following formula ##STR1## and methionine .sup.5 -enkephalin is represented by the formula ##STR2## wherein the Tyr, Phe, Met, and Leu residues are all of the L-stereochemical configuration.
2. Description of the Prior Art
R. Tomatis, et. al., IL FARMACO-ED.Sc., 34(6): 496-506 (1979) describes the synthesis of Leu-enkephalin-1-adamantylamide and Leu-[D-Ala.sup.2 ]enkephalin-1-adamantylamide. These compounds are structurally distinct from the compounds of the present invention in that they disclose 1-adamantyl amide attached to the entire enkephalin molecule whereas the present invention teaches the replacement of the amino acid in position 5 of enkephalin with an adamantyl amide.
K.Q.Do, et. al., HELVETICA CHIMICA ACTA 62(4):956-964 (1979) describes the synthesis of (S)-(+)-2-amino-3-(1-adamantyl)-propionic acid, a compound in which the phenyl radical of phenylalanine is substituted by adamantane. The present invention describes novel N-adamantane-substituted tetrapeptide amides. These compounds are analogs of enkephalin in which the 5-position is substituted by an adamantyl amide. The adamantyl amide residues of the compounds of the present invention are structurally different from (S)-(+)-2-amino-3-(1-adamantyl)-propionic acid in that the amino radical and the carboxyl radical when present are attached directly to the adamantane radical.